Evidence map›Paper›PMID 25888913›Full record

ArticleStem cell research & therapy2015

Metastatic neuroblastoma cancer stem cells exhibit flexible plasticity and adaptive stemness signaling.

Vijayabaskar Pandian, Satishkumar Ramraj, Faizan H Khan, Tasfia Azim, Natarajan Aravindan

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.0field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Cell state plasticity in neuroblastoma.EJC paediatric oncology · 2024
    Article
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  8. The role of surgery in the treatment of neuroblastoma metastases at rare sites.Journal of cancer research and clinical oncology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Vijayabaskar PandianDepartment of Radiation Oncology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 737, Oklahoma City, OK, 73104, USA. vpandian@ouhsc.edu.
Satishkumar RamrajDepartment of Radiation Oncology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 737, Oklahoma City, OK, 73104, USA. sramraj@ouhsc.edu.
Faizan H KhanDepartment of Radiation Oncology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 737, Oklahoma City, OK, 73104, USA. fkhan4@ouhsc.edu.
Tasfia AzimDepartment of Radiation Oncology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 737, Oklahoma City, OK, 73104, USA. Tasfia.Azim@OSSM.EDU.
Natarajan AravindanDepartment of Radiation Oncology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 737, Oklahoma City, OK, 73104, USA. naravind@ouhsc.edu.
University of Oklahoma Health Sciences Center · US

Funding

TUMOR RESISTANCE MECHANISMS TO ANTI-VEGF THERAPY IN PROSTATE CANCER (Sukyung Woo)P20GM103639 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI HANNAFON, BETHANY · 2012 to 2022
$21.3M
NIGMS NIH HHS 1P20GM103639-01NIGMS NIH HHS P20 GM103639
6 · The paper itself

Abstract

introductionHigh-risk neuroblastoma (HR-NB) presenting with hematogenous metastasis is one of the most difficult cancers to cure. Patient survival is poor. Aggressive tumors contain populations of rapidly proliferating clonogens that exhibit stem cell properties, cancer stem cells (CSCs). Conceptually, CSCs that evade intensive multimodal therapy dictate tumor progression, relapse/recurrence, and poor clinical outcomes. Herein, we investigated the plasticity and stem-cell related molecular response of aggressive metastatic neuroblastoma cells that fit the CSC model.

methodsWell-characterized clones of metastatic site-derived aggressive cells (MSDACs) from a manifold of metastatic tumors of clinically translatable HR-NB were characterized for their CSC fit by examining epithelial-to-mesenchymal transition (EMT) (E-cadherin, N-Cadherin), survival (NFκB P65, p50, IκB and pIκB) and drug resistance (ABCG2) by immunoblotting; pluripotency maintenance (Nanog, SOX2) by immunofluorescence; and EMT and stemness related transcription of 93 genes by QPCR profiling. Plasticity of MSDACs under sequential alternation of culture conditions with serum and serum-free stem-cell conditions was assessed by clonal expansion (BrdU incorporation), tumorosphere formation (anchorage independent growth), EMT and stemness related transcriptome (QPCR profiling) and validated with MYC, SOX2, EGFR, NOTCH1 and CXCL2 immunoblotting.

resultsHR-NB MSDACs maintained in alternated culture conditions, serum-free stem cell medium to growth medium with serum and vice versa identified its flexible revocable plasticity characteristics. We observed signatures of stem cell-related molecular responses consistent with phenotypic conversions. Successive reintroduction to the favorable niche not only regained identical EMT, self-renewal capacity, pluripotency maintenance, and other stem cell-related signaling events, but also instigated additional events depicting aggressive adaptive plasticity.

conclusionsTogether, these results demonstrated the flexible plasticity of HR-NB MSDACs that typically fit the CSC model, and further identified the intrinsic adaptiveness of the successive phenotype switching that clarifies the heterogeneity of HR-NB. Moreover, the continuous ongoing acquisition of stem cell-related molecular rearrangements may hold the key to the switch from favorable disease to HR-NB.

Indexed as

ATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CadherinsCell PlasticityCell ProliferationEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansI-kappa B KinaseNeoplasm MetastasisNeoplasm ProteinsNeoplasm Recurrence, LocalNeoplastic Stem CellsNeuroblastomaNF-kappa B p50 SubunitSignal TransductionABCG2 protein, humanATP-Binding Cassette TransportersATP Binding Cassette Transporter, Subfamily G, Member 2CadherinsI-kappa B KinaseNeoplasm ProteinsNF-kappa B p50 SubunitRELA protein, humanTranscription Factor RelA

Identifiers

PMID25888913
PMCPMC4396071
OpenAlexW2171332234

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.